Preliminary experiments performed during the current program indicate that the administration of the carcinogenic azodye 3'-methyl-4- dimethylaminoazobenzene shortens the half-life of rat liver mitochondria whereas administration of the non-carcinogenic 2-methyl-4- dimethylaminoazobenzene prolongs the half-life. Changes in the half- lives of other cell fractions, representing variations in the degradation rates of the protein populations, also occur. On the basis of the working hypothesis that aminoazodyes exert their biological effects by the selective stabilization or destabilization of heptatic proteins which may include proteins or enzymes of importance in the regulation of nucleic acid metabolism, we propose to examine whether a correlation exists between the existence and amount of labeled azodye bound to proteins of the various liver cell fractions and their half- life as estimated by the dual label method of Glass and Doyle (J. Biol. Chem. 247, 5234 (1972) ). The application of these procedures throughout the period of aminoazodye administration up to and including the cancerous stage (in the case of carcinogenic azodyes) is expected to pin-point those macromolecules which play a key role in the malignant transformation.